RIM-TD: Reducing Involuntary Movements in Participants With Tardive Dyskinesia

• Sponsor: Auspex Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02198794
• Collaborator: (none)
• Enrollment: 343
• Locations: 82
• Arms: 4
• Actual Duration (Months): 73.8
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of SD-809 in reducing the severity of abnormal involuntary movements of moderate to severe tardive dyskinesia. The purpose of part B is to establish the durability of effect of SD-809 following 1-week period of randomized withdrawal (SD-809 and placebo), followed by 12 weeks of maintenance with SD-809.

Condition or Disease	Intervention/Treatment	Phase
Tardive Dyskinesia	Drug: SD-809; Drug: Placebo	Phase 3

Detailed Description

Participants who complete study SD-809-C-18 (NCT02195700), SD-809-C-23 (NCT02291861), or any other SD-809 study will be enrolled in this study. This study include a screening period (Part A), a titration period (Part A), a long-term treatment period (Part A), a double-blind, randomized withdrawal period (Part B), treatment after completion of the randomized withdrawal period (Part B), and a post-treatment safety follow-up period (Part A and Part B). EU participants who complete Part B will be invited to participate in Part C.

Study Design

• Study Type: Interventional
• Actual Enrollment: 343 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Long-Term Safety Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia
• Actual Study Start Date: Oct 20, 2014
• Actual Primary Completion Date: Dec 6, 2019
• Actual Study Completion Date: Dec 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: SD-809 Participants will receive SD-809 orally twice daily (BID) starting at 12 mg/day, which will be titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who decline to participate in Part B, will continue at their stable dose of SD-809 BID up to Week 158.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717
Placebo Comparator: Part B: Placebo Participants will receive placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter will receive SD-809 (stable dose) for 12 weeks.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717 ; Drug: Placebo; Placebo matching to SD-809 will be administered per schedule specified in the arm.
Active Comparator: Part B: SD-809 Participants will receive SD-809 (stable dose) for 1 week in randomized withdrawal period and will continue to receive the same dose of SD-809 for an additional 12 weeks.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717
Experimental: Part C: SD-809 EU participants who complete Part B and willing to continue in the study will continue treatment with SD-809 for 52 weeks at the dose administered during the 12-week open-label period of Part B.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717

Outcome Measures

Primary Outcome Measures

1. Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal [Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days)]

   AEs were analyzed as one group combined for parts A and B per planned analysis. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=prevents normal daily activities. Drug-related TEAEs: TEAEs with possible, probable, or definite relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A treatment-emergent AE was defined as an AE that began after the first administration of study medication or existing AEs that worsened after the first dose of study medication. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

2. Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating [Day 1 of Part B, Day 7 of Part B]

   The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

Secondary Outcome Measures

1. Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating [Baseline, Week 145]

   The AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

2. Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating [Baseline, Week 158]

   The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

3. Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating [Baseline, Week 145]

   The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

4. Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating [Baseline, Week 158]

   The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

5. Part A: Percentage of Participants Who Had a 50% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating [Baseline to Week 145]

   The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

6. Part A: Percentage of Participants Who Had a 70% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating [Baseline to Week 145]

   The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

7. Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating [Baseline, Week 145]

   The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. Items 8 to 10 deal with global severity as judged by the examiner, and the participant's awareness of the movements and the distress associated with them. Item 8 (used as an overall severity index indicating severity of abnormal movements) was rated on a 5-point anchored scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 9 and 10 (provide additional information with regard to participant's incapacitation due to abnormal movements and participant's awareness of abnormal movements) were rated on a 5-point anchored scale ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Higher scores indicated more severe disease.

8. Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC) [Baseline up to Week 145]

   A treatment success was defined as much or very much improved on the CGIC from baseline of this study. The CGIC is a single-item questionnaire that asks the investigator to assess a participant's TD symptoms at specific visits/weeks after initiating therapy. The CGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.

9. Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC) [Baseline up to Week 145]

   A treatment success was defined as much or very much improved on the PGIC from baseline of this study. The PGIC is single-item questionnaire that asks the participant to assess their TD symptoms at specific visits/weeks after initiating therapy. The PGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.

10. Part A: Change From Baseline in Modified CDQ-24 Score at Week 158 [Baseline, Week 158]

    The CDQ-24 is a disease-specific quality of life questionnaire developed for use in participants with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ-24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains were evaluated in the mCDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by participants on a scale of 0 = never or no impairment to 4 = always or very severe impairment. Total score ranged from 0 - 96, with higher score indicative of severe impairment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of using a dopamine receptor antagonist for at least 3 months

• Clinical diagnosis of tardive dyskinesia and has had symptoms for at least 3 months prior to screening

• Participant has successfully completed a controlled study of SD-809 for treatment of moderate to severe tardive dyskinesia

• Participants with underlying psychiatric diagnosis are stable and have no change in psychoactive medications

• Have a mental health provider and does not anticipate any changes to treatment regimen in the next 3 months

• History of being compliant with prescribed medications

• Able to swallow study drug whole

• Be in good general health and is expected to attend all study visits and complete study assessments

• Female participants must not be pregnant and agree to an acceptable method of contraception

Exclusion Criteria:

• Currently receiving medication for the treatment of tardive dyskinesia

• Have a neurological condition other than tardive dyskinesia that may interfere with assessing the severity of dyskinesias

• Have a serious untreated or undertreated psychiatric illness

• Have recent history or presence of violent behavior

• Have unstable or serious medical illness

• Have evidence of hepatic impairment

• Have evidence of renal impairment

• Have known allergy to any component of SD-809 or tetrabenazine

• Has participated in an investigational drug or device trial (other than Study C-18, Study C-23, or any other eligible TEV-50717 parent study) and received study drug within 30 days

• Have acknowledged use of illicit drugs

• Have a history of alcohol or substance abuse in the previous 12 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 145	Tuscaloosa	Alabama	United States	35404
2	Teva Investigational Site 107	Anaheim	California	United States	92804
3	Teva Investigational Site 108	Anaheim	California	United States	92805
4	Teva Investigational Site 123	Glendale	California	United States	91206
5	Teva Investigational Site 160	Irvine	California	United States	92614
6	Teva Investigational Site 176	Loma Linda	California	United States	92354
7	Teva Investigational Site 121	Los Angeles	California	United States	90033
8	Teva Investigational Site 147	Los Angeles	California	United States	90095-1769
9	Teva Investigational Site 174	Norwalk	California	United States	90650
10	Teva Investigational Site 130	Oceanside	California	United States	92056
11	Teva Investigational Site 102	Orange	California	United States	92868
12	Teva Investigational Site 104	San Bernardino	California	United States	92408
13	Teva Investigational Site 110	San Diego	California	United States	92108
14	Teva Investigational Site 169	San Rafael	California	United States	94901
15	Teva Investigational Site 129	Englewood	Colorado	United States	80113
16	Teva Investigational Site 139	New Haven	Connecticut	United States	06519
17	Teva Investigational Site 156	Washington	District of Columbia	United States	20007
18	Teva Investigational Site 157	Boca Raton	Florida	United States	33486
19	Teva Investigational Site 117	Gainesville	Florida	United States	32607
20	Teva Investigational Site 150	Lake City	Florida	United States	32025
21	Teva Investigational Site 153	Miami	Florida	United States	33135
22	Teva Investigational Site 162	Miami	Florida	United States	33165
23	Teva Investigational Site 112	Orlando	Florida	United States	32803
24	Teva Investigational Site 144	Port Charlotte	Florida	United States	33980
25	Teva Investigational Site 155	Augusta	Georgia	United States	30912
26	Teva Investigational Site 165	Decatur	Georgia	United States	30033
27	Teva Investigational Site 131	Chicago	Illinois	United States	60611
28	Teva Investigational Site 154	Baltimore	Maryland	United States	21287
29	Teva Investigational Site 101	Glen Burnie	Maryland	United States	21061
30	Teva Investigational Site 118	Creve Coeur	Missouri	United States	63141
31	Teva Investigational Site 142	Kansas City	Missouri	United States	64108
32	Teva Investigational Site 175	Saint Louis	Missouri	United States	63104
33	Teva Investigational Site 161	Saint Louis	Missouri	United States	63109
34	Teva Investigational Site 178	Lincoln	Nebraska	United States	68526-9467
35	Teva Investigational Site 128	Albuquerque	New Mexico	United States	87106
36	Teva Investigational Site 146	Raleigh	North Carolina	United States	27610
37	Teva Investigational Site 114	Garfield Heights	Ohio	United States	44125
38	Teva Investigational Site 133	Charleston	South Carolina	United States	29425
39	Teva Investigational Site 149	Memphis	Tennessee	United States	38163
40	Teva Investigational Site 151	Fort Worth	Texas	United States	76104
41	Teva Investigational Site 115	Salt Lake City	Utah	United States	84105
42	Teva Investigational Site 141	Salt Lake City	Utah	United States	84108
43	Teva Investigational Site 167	Richland	Washington	United States	99352
44	Teva Investigational Site 166	Waukesha	Wisconsin	United States	53188
45	Teva Investigational Site 559	Havirov		Czechia	736 01
46	Teva Investigational Site 556	Hostivice		Czechia	999999
47	Teva Investigational Site 535	Litomerice		Czechia	412 01
48	Teva Investigational Site 557	Plzen		Czechia	312 00
49	Teva Investigational Site 533	Prague 10		Czechia	100 00
50	Teva Investigational Site 530	Prague 6		Czechia	16000
51	Teva Investigational Site 502	Gera		Germany	07551
52	Teva Investigational Site 504	Mainz		Germany	55131
53	Teva Investigational Site 540	Balassagyarmat		Hungary	999999
54	Teva Investigational Site 538	Budapest		Hungary	1135
55	Teva Investigational Site 541	Budapest		Hungary	1148
56	Teva Investigational Site 539	Doba		Hungary	8482
57	Teva Investigational Site 546	Gyor		Hungary	H-9024
58	Teva Investigational Site 545	Kalocsa		Hungary	6300
59	Teva Investigational Site 514	Belchatow		Poland	97-400
60	Teva Investigational Site 554	Bialystok		Poland	15-756
61	Teva Investigational Site 510	Bydgoszcz		Poland	85-015
62	Teva Investigational Site 519	Bydgoszcz		Poland	85-080
63	Teva Investigational Site 536	Bydgoszcz		Poland	85-156
64	Teva Investigational Site 523	Chelmno		Poland	86-200
65	Teva Investigational Site 517	Choroszcz		Poland	16-070
66	Teva Investigational Site 513	Gdansk		Poland	80-952
67	Teva Investigational Site 512	Katowice		Poland	40-097
68	Teva Investigational Site 552	Katowice		Poland	40-123
69	Teva Investigational Site 520	Krakow		Poland	30-349
70	Teva Investigational Site 509	Krakow		Poland	31-505
71	Teva Investigational Site 508	Lodz		Poland	90-130
72	Teva Investigational Site 511	Lublin		Poland	20-064
73	Teva Investigational Site 524	Lublin		Poland	20-831
74	Teva Investigational Site 549	Olsztyn		Poland	10-443
75	Teva Investigational Site 522	Torun		Poland	87-100
76	Teva Investigational Site 550	Warszawa		Poland	00-465
77	Teva Investigational Site 516	Wroclaw		Poland	50-227
78	Teva Investigational Site 529	Bratislava		Slovakia	826 06
79	Teva Investigational Site 525	Hronovce		Slovakia	935 61
80	Teva Investigational Site 527	Kosice		Slovakia	04017
81	Teva Investigational Site 528	Rimavska Sobota		Slovakia	979 12
82	Teva Investigational Site 526	Roznava		Slovakia	04801

Sponsors and Collaborators

• Auspex Pharmaceuticals, Inc.

Investigators

• Study Director: Teva Medical Expert, M.D., Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

• Study Protocol - May 2, 2018
• Statistical Analysis Plan - Dec 3, 2019

More Information

Publications

None provided.

• Responsible Party: Auspex Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02198794
• Other Study ID Numbers: SD-809-C-20; 2014-001891-73
• First Posted: Jul 24, 2014
• Last Update Posted: Apr 1, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Auspex Pharmaceuticals, Inc.: Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms
• Additional relevant MeSH terms: Dyskinesias; Tardive Dyskinesia

Study Results

Participant Flow

Recruitment Details	343 participants who completed previous SD-809 studies, including study SD-809-C-18 (NCT02195700) or SD-809-C-23 (NCT02291861) were enrolled and 337 participants were eligible for analysis. 6 participants were not evaluable and were excluded from the analysis due to site data integrity issues as reported to the United States Food and Drug Administration (US FDA).
Pre-assignment Detail	Study included 3 parts: A, B, and C. Participants in Part A who were on a stable dose for ≥4 weeks after a 6-week titration, were invited to participate in Part B. Participants who are noted as "Completed" for Part A: completed the study in Part A plus continued in Part B. EU participants who completed Part B were invited to participate in Part C.

Arm/Group Title	SD-809	Part B: Placebo	Part B: SD-809	Part C: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Participants received placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter received SD-809 (stable dose) for 12 weeks.	Participants received SD-809 (stable dose) for 1 week in randomized withdrawal period and continued to receive the same dose of SD-809 for an additional 12 weeks.	EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Period Title: Part A: Open-Label (158 Weeks)
STARTED	337	0	0	0
Received at Least 1 Dose of Study Drug	337	0	0	0
Intent-to-Treat (ITT) Population	337	0	0	0
Participants Who Participated in Part A But Not in Part B	195	0	0	0
Participants Who Agreed to Continue in Part B	142	0	0	0
COMPLETED	32	0	0	0
NOT COMPLETED	305	0	0	0
Period Title: Part A: Open-Label (158 Weeks)
STARTED	0	71	71	0
Randomized Withdrawal mITT Population	0	63	65	0
COMPLETED	0	66	68	0
NOT COMPLETED	0	5	3	0
Period Title: Part A: Open-Label (158 Weeks)
STARTED	0	0	0	80
COMPLETED	0	0	0	73
NOT COMPLETED	0	0	0	7

Baseline Characteristics

Arm/Group Title	SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Overall Participants	337
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.9 (10.65)
Sex: Female, Male (Count of Participants)
Female	188 55.8%
Male	149 44.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	28 8.3%
Not Hispanic or Latino	300 89%
Unknown or Not Reported	9 2.7%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaskan Native	1 0.3%
Asian	2 0.6%
Black	69 20.5%
White	264 78.3%
Other	1 0.3%
Total Motor Abnormal Involuntary Movement Scale (AIMS) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	10.7 (4.68)
AIMS Individual Items (8-10) Scores (units on a scale) [Mean (Standard Deviation) ]
Severity of abnormal movements	2.6 (0.78)
Incapacitation due to abnormal movements	2.0 (1.07)
Participant's awareness of abnormal movements	2.2 (1.08)
Modified Craniocervical Dystonia Questionnaire 24 (CDQ-24) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	29.2 (18.96)

Outcome Measures

1. Primary Outcome

Title	Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal
Description	AEs were analyzed as one group combined for parts A and B per planned analysis. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=prevents normal daily activities. Drug-related TEAEs: TEAEs with possible, probable, or definite relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A treatment-emergent AE was defined as an AE that began after the first administration of study medication or existing AEs that worsened after the first dose of study medication. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were administered any study drug.

Arm/Group Title	SD-809	Part C: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Measure Participants	337	80
Any TEAEs	269 79.8%	23 NaN
Serious TEAEs	68 20.2%	5 NaN
Severe TEAEs	57 16.9%	3 NaN
Drug-Related TEAEs	154 45.7%	3 NaN
TEAEs Leading to Withdrawal From Study	42 12.5%	3 NaN

2. Primary Outcome

Title	Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Time Frame	Day 1 of Part B, Day 7 of Part B

Outcome Measure Data

Analysis Population Description

The randomized withdrawal modified intent-to-treat (mITT) population included all participants enrolled in Part B who received study drug during the randomized withdrawal period and had a total motor AIMS score as assessed by blinded central video rating at both the pre-withdrawal visit and the post-withdrawal visit.

Arm/Group Title	Part B: Placebo	Part B: SD-809
Arm/Group Description	Participants received placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter received SD-809 (stable dose) for 12 weeks.	Participants received SD-809 (stable dose) for 1 week in randomized withdrawal period and continued to receive the same dose of SD-809 for an additional 12 weeks.
Measure Participants	63	65
Pre-withdrawal	5.7 (0.55)	5.0 (0.49)
Change at Post-withdrawal	0.6 (0.28)	0 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809, Part C: SD-809
	Comments	The statistical model was an analysis of covariance (ANCOVA) with treatment group and dopamine receptor antagonist status at the pre-withdrawal visit as fixed effects and the pre-withdrawal visit value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.121
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square (LS) Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.42 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Time Frame	Baseline, Week 145

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	160
Mean (Standard Error) [units on a scale]	-6.6 (0.37)

4. Secondary Outcome

Title	Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	34
Mean (Standard Error) [units on a scale]	-6.3 (0.85)

5. Secondary Outcome

Title	Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Time Frame	Baseline, Week 145

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	159
Mean (Standard Error) [percent change]	-57.0 (2.43)

6. Secondary Outcome

Title	Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	34
Mean (Standard Error) [percent change]	-54.9 (6.76)

7. Secondary Outcome

Title	Part A: Percentage of Participants Who Had a 50% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Time Frame	Baseline to Week 145

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	159
Number [percentage of participants]	67 19.9%

8. Secondary Outcome

Title	Part A: Percentage of Participants Who Had a 70% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Time Frame	Baseline to Week 145

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	159
Number [percentage of participants]	42 12.5%

9. Secondary Outcome

Title	Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating
Description	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. Items 8 to 10 deal with global severity as judged by the examiner, and the participant's awareness of the movements and the distress associated with them. Item 8 (used as an overall severity index indicating severity of abnormal movements) was rated on a 5-point anchored scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 9 and 10 (provide additional information with regard to participant's incapacitation due to abnormal movements and participant's awareness of abnormal movements) were rated on a 5-point anchored scale ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Higher scores indicated more severe disease.
Time Frame	Baseline, Week 145

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	160
Severity of abnormal movements	-1.3 (0.07)
Incapacitation due to abnormal movements	-1.3 (0.08)
Participant's awareness of abnormal movements	-1.3 (0.09)

10. Secondary Outcome

Title	Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC)
Description	A treatment success was defined as much or very much improved on the CGIC from baseline of this study. The CGIC is a single-item questionnaire that asks the investigator to assess a participant's TD symptoms at specific visits/weeks after initiating therapy. The CGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.
Time Frame	Baseline up to Week 145

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	160
Number [percentage of participants]	73 21.7%

11. Secondary Outcome

Title	Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC)
Description	A treatment success was defined as much or very much improved on the PGIC from baseline of this study. The PGIC is single-item questionnaire that asks the participant to assess their TD symptoms at specific visits/weeks after initiating therapy. The PGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.
Time Frame	Baseline up to Week 145

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	161
Number [percentage of participants]	63 18.7%

12. Secondary Outcome

Title	Part A: Change From Baseline in Modified CDQ-24 Score at Week 158
Description	The CDQ-24 is a disease-specific quality of life questionnaire developed for use in participants with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ-24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains were evaluated in the mCDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by participants on a scale of 0 = never or no impairment to 4 = always or very severe impairment. Total score ranged from 0 - 96, with higher score indicative of severe impairment.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Measure Participants	39
Mean (Standard Error) [units on a scale]	-6.3 (2.61)

Adverse Events

Time Frame	Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days)
Adverse Event Reporting Description	Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Arm/Group Title	Part A and Part B Participants		Part C: SD-809
Arm/Group Description	Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158. Participants who agreed to participate in Part B, received SD-809 or placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter received SD-809 (stable dose) for 12 weeks.		EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
All Cause Mortality
	Part A and Part B Participants		Part C: SD-809
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/337 (2.4%)		2/80 (2.5%)
Serious Adverse Events
	Part A and Part B Participants		Part C: SD-809
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/337 (20.2%)		5/80 (6.3%)
Blood and lymphatic system disorders
Anaemia	1/337 (0.3%)	1	0/80 (0%)	0
Cardiac disorders
Angina pectoris	1/337 (0.3%)	1	0/80 (0%)	0
Cardiac arrest	1/337 (0.3%)	1	0/80 (0%)	0
Cardiac failure	2/337 (0.6%)	2	1/80 (1.3%)	1
Cardiopulmonary failure	1/337 (0.3%)	1	0/80 (0%)	0
Cardiovascular insufficiency	2/337 (0.6%)	2	0/80 (0%)	0
Myocardial infarction	1/337 (0.3%)	1	0/80 (0%)	0
Ventricular tachycardia	1/337 (0.3%)	1	0/80 (0%)	0
Acute myocardial infarction	0/337 (0%)	0	1/80 (1.3%)	1
Gastrointestinal disorders
Diarrhoea	1/337 (0.3%)	2	0/80 (0%)	0
Gastric ulcer perforation	1/337 (0.3%)	1	0/80 (0%)	0
Pancreatic duct stenosis	1/337 (0.3%)	1	0/80 (0%)	0
General disorders
Non-cardiac chest pain	1/337 (0.3%)	1	0/80 (0%)	0
Hepatobiliary disorders
Cholelithiasis	1/337 (0.3%)	1	0/80 (0%)	0
Hepatic cyst	1/337 (0.3%)	1	0/80 (0%)	0
Liver disorder	1/337 (0.3%)	1	0/80 (0%)	0
Infections and infestations
Appendicitis	1/337 (0.3%)	1	0/80 (0%)	0
Cholecystitis infective	1/337 (0.3%)	1	0/80 (0%)	0
Colonic abscess	1/337 (0.3%)	1	0/80 (0%)	0
Cystitis	1/337 (0.3%)	1	0/80 (0%)	0
Diverticulitis	1/337 (0.3%)	1	0/80 (0%)	0
Gangrene	1/337 (0.3%)	1	0/80 (0%)	0
Gastroenteritis	1/337 (0.3%)	1	0/80 (0%)	0
Mycobacterium avium complex infection	1/337 (0.3%)	1	0/80 (0%)	0
Pneumonia	4/337 (1.2%)	4	1/80 (1.3%)	1
Pulmonary tuberculosis	1/337 (0.3%)	1	0/80 (0%)	0
Sepsis	1/337 (0.3%)	1	0/80 (0%)	0
Septic shock	1/337 (0.3%)	1	0/80 (0%)	0
Urinary tract infection	2/337 (0.6%)	3	0/80 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/337 (0.3%)	1	0/80 (0%)	0
Burns second degree	1/337 (0.3%)	1	0/80 (0%)	0
Carbon monoxide poisoning	1/337 (0.3%)	1	0/80 (0%)	0
Facial bones fracture	1/337 (0.3%)	1	0/80 (0%)	0
Femur fracture	1/337 (0.3%)	1	0/80 (0%)	0
Humerus fracture	1/337 (0.3%)	1	0/80 (0%)	0
Intentional overdose	1/337 (0.3%)	1	0/80 (0%)	0
Procedural pain	1/337 (0.3%)	1	0/80 (0%)	0
Spinal fracture	1/337 (0.3%)	1	0/80 (0%)	0
Tendon rupture	1/337 (0.3%)	1	0/80 (0%)	0
Thermal burn	1/337 (0.3%)	1	0/80 (0%)	0
Tibia fracture	1/337 (0.3%)	2	0/80 (0%)	0
Traumatic haemothorax	1/337 (0.3%)	1	0/80 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/337 (0.3%)	1	1/80 (1.3%)	1
Diabetic ketoacidosis	1/337 (0.3%)	1	0/80 (0%)	0
Failure to thrive	1/337 (0.3%)	1	0/80 (0%)	0
Hypoglycaemia	1/337 (0.3%)	1	0/80 (0%)	0
Hyponatraemia	1/337 (0.3%)	1	0/80 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/337 (0.3%)	1	0/80 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal squamous cell carcinoma	1/337 (0.3%)	1	0/80 (0%)	0
Benign breast neoplasm	1/337 (0.3%)	1	0/80 (0%)	0
Breast cancer	1/337 (0.3%)	1	0/80 (0%)	0
Prostate cancer	1/337 (0.3%)	1	0/80 (0%)	0
Squamous cell carcinoma of skin	1/337 (0.3%)	1	0/80 (0%)	0
Squamous cell carcinoma of the tongue	1/337 (0.3%)	1	0/80 (0%)	0
Transitional cell carcinoma	1/337 (0.3%)	1	0/80 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/337 (0.3%)	1	0/80 (0%)	0
Epilepsy	1/337 (0.3%)	1	0/80 (0%)	0
Generalised non-convulsive epilepsy	1/337 (0.3%)	1	0/80 (0%)	0
Migraine	1/337 (0.3%)	1	0/80 (0%)	0
Transient ischaemic attack	1/337 (0.3%)	1	0/80 (0%)	0
Psychiatric disorders
Anxiety	1/337 (0.3%)	1	0/80 (0%)	0
Depression	2/337 (0.6%)	2	0/80 (0%)	0
Depressive symptom	1/337 (0.3%)	1	0/80 (0%)	0
Homicidal ideation	1/337 (0.3%)	1	0/80 (0%)	0
Hypomania	2/337 (0.6%)	2	0/80 (0%)	0
Mania	2/337 (0.6%)	2	0/80 (0%)	0
Mental status changes	1/337 (0.3%)	1	0/80 (0%)	0
Psychotic disorder	2/337 (0.6%)	2	0/80 (0%)	0
Schizoaffective disorder	2/337 (0.6%)	4	0/80 (0%)	0
Schizophrenia	5/337 (1.5%)	5	0/80 (0%)	0
Suicidal ideation	3/337 (0.9%)	3	0/80 (0%)	0
Suicide attempt	1/337 (0.3%)	1	0/80 (0%)	0
Schizophrenia, paranoid type	0/337 (0%)	0	1/80 (1.3%)	1
Renal and urinary disorders
Renal failure acute	2/337 (0.6%)	2	0/80 (0%)	0
Stress urinary incontinence	1/337 (0.3%)	1	0/80 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/337 (0.3%)	2	1/80 (1.3%)	1
Chronic obstructive pulmonary disease	4/337 (1.2%)	8	0/80 (0%)	0
Interstitial lung disease	1/337 (0.3%)	1	0/80 (0%)	0
Pneumonia aspiration	1/337 (0.3%)	1	0/80 (0%)	0
Pulmonary embolism	1/337 (0.3%)	1	0/80 (0%)	0
Respiratory failure	1/337 (0.3%)	1	0/80 (0%)	0
Vascular disorders
Deep vein thrombosis	1/337 (0.3%)	1	0/80 (0%)	0
Iliac artery occlusion	1/337 (0.3%)	1	0/80 (0%)	0
Peripheral ischaemia	1/337 (0.3%)	1	0/80 (0%)	0
Circulatory collapse	0/337 (0%)	0	1/80 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Part A and Part B Participants		Part C: SD-809
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	172/337 (51%)		5/80 (6.3%)
Gastrointestinal disorders
Diarrhoea	27/337 (8%)	32	0/80 (0%)	0
Infections and infestations
Nasopharyngitis	20/337 (5.9%)	28	2/80 (2.5%)	2
Urinary tract infection	31/337 (9.2%)	56	0/80 (0%)	0
Injury, poisoning and procedural complications
Fall	18/337 (5.3%)	23	0/80 (0%)	0
Investigations
Weight decreased	32/337 (9.5%)	34	0/80 (0%)	0
Nervous system disorders
Dyskinesia	22/337 (6.5%)	29	2/80 (2.5%)	2
Headache	24/337 (7.1%)	31	0/80 (0%)	0
Somnolence	34/337 (10.1%)	41	0/80 (0%)	0
Psychiatric disorders
Anxiety	41/337 (12.2%)	51	0/80 (0%)	0
Depression	35/337 (10.4%)	45	0/80 (0%)	0
Vascular disorders
Hypertension	23/337 (6.8%)	25	1/80 (1.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.